Shibata Kiyosumi, Kajiyama Hiroaki, Mizokami Yayoi, Ino Kazuhiko, Nomura Seiji, Mizutani Shigehiko, Terauchi Mikio, Kikkawa Fumitaka
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
Gynecol Oncol. 2005 Jul;98(1):11-8. doi: 10.1016/j.ygyno.2005.03.043.
Increased glucose consumption is a characteristic of malignant cells. Glucose is transported into the cell via facilitative glucose transporters, which are known to be members of a supergene family. The insulin-responsive GLUT4 isoform is expressed almost exclusively in insulin target tissues. P-LAP is a cell surface aminopeptidase, and is a synonym for oxytocinase. P-LAP is also referred to as insulin-regulated membrane aminopeptidase (IRAP) associated with GLUT4-containing vesicle. The authors evaluated P-LAP and GLUT4 expression in benign, borderline, and malignant ovarian epithelia.
Histologic sections of formalin-fixed, paraffin-embedded specimens from 11 patients with benign serous or mucinous cystadenomas, 14 patients with serous or mucinous borderline tumors, and 80 patients with epithelial-ovarian adenocarcinomas (29 serous, 17 endometrioid, 14 mucinous, and 20 clear cell adenocarcinomas) were stained for P-LAP and GLUT4 using each polyclonal antibody. Expressions of P-LAP and GLUT-4 in ovarian cancer cells were detected by Western blotting.
P-LAP immunoreactivity was detected in 2 of 11 benign cystadenomas. None of the 11 benign ovarian tumors showed any immunoreactivity for GLUT4. Seven of 14 borderline tumors demonstrated P-LAP immunoreactivity, while 5 of 14 borderline tumors demonstrated GLUT4 immunoreactivity. P-LAP was expressed in 23 of 29 in serous, 15 of 17 endometrioid, 13 of 14 mucinous, and all clear-cell adenocarcinomas. The tendency toward increased P-LAP expression with advancing grade was observed in serous adenocarcinomas. GLUT4 was expressed in 13 of 29 serous, 13 of 17 endometrioid, 13 of 14 mucinous, and 18 of 20 clear-cell adenocarcinomas. In invasive carcinomas, there was a direct correlation between P-LAP immunoreactivity and GLUT4 immunoreactivity (correlation coefficient [r] = 0.58; P < 0.01). Furthermore, P-LAP overexpression in SKOV3 cells induced the GLUT4 expression.
P-LAP and GLUT4 are available not only for the evaluation of ovarian epithelial malignancy, but also as targets for molecular therapy. Further study to investigate the roles of P-LAP and GLUT4 in ovarian carcinoma is needed.
葡萄糖消耗增加是恶性细胞的一个特征。葡萄糖通过易化葡萄糖转运蛋白进入细胞，这些转运蛋白是一个超基因家族的成员。胰岛素反应性葡萄糖转运蛋白4（GLUT4）亚型几乎只在胰岛素靶组织中表达。胎盘碱性磷酸酶（P-LAP）是一种细胞表面氨肽酶，是催产素酶的同义词。P-LAP也被称为与含GLUT4囊泡相关的胰岛素调节膜氨肽酶（IRAP）。作者评估了P-LAP和GLUT4在良性、交界性和恶性卵巢上皮中的表达。
对11例良性浆液性或黏液性囊腺瘤患者、14例浆液性或黏液性交界性肿瘤患者以及80例上皮性卵巢腺癌患者（29例浆液性、17例子宫内膜样、14例黏液性和20例透明细胞腺癌）的福尔马林固定、石蜡包埋标本的组织切片，使用每种多克隆抗体进行P-LAP和GLUT4染色。通过蛋白质印迹法检测卵巢癌细胞中P-LAP和GLUT-4的表达。
11例良性囊腺瘤中有2例检测到P-LAP免疫反应性。11例良性卵巢肿瘤中无一例显示出对GLUT4的免疫反应性。14例交界性肿瘤中有7例显示P-LAP免疫反应性，而14例交界性肿瘤中有5例显示GLUT4免疫反应性。P-LAP在29例浆液性癌中的23例、17例子宫内膜样癌中的15例、14例黏液性癌中的13例以及所有透明细胞腺癌中均有表达。在浆液性腺癌中观察到随着分级升高P-LAP表达增加的趋势。GLUT4在29例浆液性癌中的13例、17例子宫内膜样癌中的13例、14例黏液性癌中的13例以及20例透明细胞腺癌中的18例中有表达。在浸润性癌中，P-LAP免疫反应性与GLUT4免疫反应性之间存在直接相关性（相关系数[r]=0.58；P<0.01）。此外，SKOV3细胞中P-LAP的过表达诱导了GLUT4的表达。
P-LAP和GLUT4不仅可用于评估卵巢上皮恶性肿瘤，还可作为分子治疗的靶点。需要进一步研究以探讨P-LAP和GLUT4在卵巢癌中的作用。
